In a series of recent papers, a new covariant formalism was introduced to treat inhomogeneities in any spacetime. The variables introduced in these papers are gauge-invariant with respect to a Robertson-Walker background spacetime because they vanish identically in such models, and they have a transparent physical meaning. Exact evolution equations were found for these variables, and the linearized form of these equations were obtained, showing that they give the standard results for a barotropic perfect fluid. In this paper we extend this formalism to the general case of multicomponent fluid sources with interactions between them. We show, using the tilted formalism of King and Ellis, (1973) that choosing either the energy frame or the particle frame gives rise to a set of physically well-defined covariant and gauge-invariant variables which describe density and velocity perturbations, both for the total fluid and its constituent components. We then derive a complete set of equations for these variables and show, through harmonic analysis, that they are equivalent to those of Bardeen (1980) and of Kodama and Sasaki (1984). We discuss a number of interesting applications, including the case where the universe is filled with a mixture of baryons and radiation, coupled through Thomson scattering, and we derive solutions for the density and velocity perturbations in the large-scale limit. We also correct a number of errors in the previous literature.